1. Field of the Invention
This invention relates to a process for producing 4-homoisotwistane-3-carboxylic acid which belongs to tricyclo carboxylic acids.
2. Description of the Prior Art
4-homoisotwistane-3-carboxylic acid is a known compound found by the present inventors (refer to Japanese Patent Publication No. 20979/1978) and esters of 4-homoisotwistane-3-carboxylic acid derived therefrom are compounds which are known to have anti-virus activity (refer to Japanese Patent Publication No. 8494/1980).
Heretofore, the 4-homoisotwistane-3-carboxylic acid (I) has been synthesized by way of a very much troublesome synthesizing process as shown by the following schemes (yield from the starting material: 15%). However, cyclohexadiene as the starting material can not be obtained industrially inexpensively now, and this synthetic process has been very much inconveninent. ##STR2##
In view of the above, the inventors of the present application have previously found a process for synthesizing 4-homoisotwistane-3-carboxylic acid, said process comprising reacting 8-hydroxy-methyl-tricyclo [5.2.1.0.sup.2,6 ]decane, which can be synthesized from industrially available dicyclopentadiene, with carbon monoxide and water, or with formic acid in the presence of sulfuric acid thereby transforming the skelton thereof while carboxylating the 3-position of the 4-homoisotwistane simultaneously, and filed a patent application (Japanese Patent Application No. 8814/1981). However, as shown in the following schemes, the reaction proceeds through a multistep of skelton transformation and, therefore, the intermediates are liable to be subjected to side reactions and the yield has actually been as low as about 20%. ##STR3##
Such conventional carboxylating reactions are generally referred to as Koch reactions, which have the following defects inherent to the Koch reactions.
Among the Koch reactions, a CO pressure method of reacting an alcohol or olefin with carbon monoxide and water in the presence of an inorganic strongly acidic catalyst, involves the following drawbacks; (1) since it is important to increase the pressure of carbon monoxide (CO) for suppressing the formation of tars in order to improve the yield, it is required to use a pressure-proof vessel, which means a restriction in view of the facility; (2) it requires energy for pressurizing the carbon mono-oxide; and (3) since the reaction is carried out in the presence of a water-containing acid catalyst, special materials are required for the autoclave, which causes an increase in the installation cost. Among the Koch reactions, a formic acid method of reacting an alcohol or olefin with formic acid in the presence of an inorganic strongly acidic catalyst, although being free from the drawbacks as in the CO pressure method since the reaction can be taken place under ambient pressure, involves several drawbacks in that (1) the yield will be decreased unless formic acid is used in a large excess to the alcohol or olefin; (2) the excess formic acid in the reaction system is decomposed by the acid into water and carbon monoxide, with the resulting water reducing the catalyst activity, and the carbon monoxide being discharged as a gas to cause undesired circumstantial problems; (3) since the excess formic acid can not be recovered, it results in disadvantages in view of the cost; and (4) since formic acid is often less miscible with olefins and alcohols, it requires to introduce the formic acid and the reaction substrate at an accurate dropping rate to the reaction system for preventing the decrease in the yield, which renders the procedures much complicated.
Further, one of the common problems to those processes is that acid has to be used in an extremely large amount. If the acid can not be recovered, the disposition for the great amount of wasted acid causes a significant problem in view of the production step. Even if the acid can be recovered, the use of such great amount of acid inevitably leads to the disadvantage of decreasing the charge amount per one reaction cycle.
As described above, the conventional process for producing 4-homoisotwistane-3-carboxylic acid has involved a variety of problems both in the yield and the reaction process and has not yet been completely satisfactory.